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This early influence of spatial attention may be possible because retinotopic mapping of the visual system means that the brain encodes space very early-as early as at the retina-and space is a strong defining feature of relevant versus irrelevant environmental events anxiety symptoms vs heart attack buy tofranil 25mg fast delivery. Where anxiety ulcer discount tofranil 50 mg with mastercard, within the visual sensory hierarchy, are these earliest effects of selective visuospatial attention taking place and what do they represent The P1 attention effect has a latency of about 70 ms from stimulus onset, and it is sensitive to changes in physical stimulus parameters, such as location in the visual field and stimulus luminance. Then the responses to the same physical stimuli, such as the white rectangle being flashed to left visual hemifield in the figure, are compared when they are attended and ignored. Their names reflect their voltage (P = positive; N = negative) and their order of appearance. Taken together, these clues suggest that the P1 wave is a sensory wave generated by neural activity in the visual cortex, and therefore, its sensitivity to spatial attention supports early selection models of attention. This combined response produces a large enough signal to propagate through the skull to be recorded on the human scalp. Can the effect of attention be detected in the response of single visual neurons in the cortex As a good neuroscientist, you immediately think, "I wonder how my spatial attention, focused on this Maserati, is affecting my neurons in my visual cortex right now The scientists investigated how visuospatial selective attention affected the firing rates of individual neurons in the visual cortex of monkeys. Using single-cell recording, they first recorded and characterized the responses of single neurons in extrastriate visual area V4 (ventral stream area) to figure out what regions of the visual field they coded (receptive field location) and which specific stimulus features the neurons responded to most vigorously. The team found, for example, that neurons in V4 fired robustly in response to a single-colored, oriented bar stimulus. Over a period of several months, the researchers had previously trained the monkeys to fixate on a central spot on a monitor, to covertly attend to the stimulus at one location in the visual field, and to perform a task related to it while ignoring the other stimulus. Responses of single neurons were recorded and compared under two conditions: when the monkey attended the preferred (red horizontal bar) stimulus, and when it instead attended the non-preferred (green vertical bar) stimulus that was located a short distance away. Because the two stimuli (attended and ignored) were positioned in different locations, the task can be characterized as a spatial attention task. Neural Mechanisms of Attention and Perceptual Selection 289 When the red stimulus was attended, it elicited a stronger response (more action potentials fired per second) in the corresponding V4 neuron that preferred red horizontal bars than when the red stimulus was ignored while attending the green vertical bar positioned at another location. Thus, spatial selective attention affected the firing rates of V4 neurons (Figure 7. Several studies have replicated the attention effects observed by Moran and Desimone in V4 and have extended this finding to other visual areas, including later stages of the ventral pathway in the inferotemporal region. Researchers also investigated whether attention affected even earlier steps in visual processing- in primary visual cortex (V1), for example. Carrie McAdams and Clay Reid (2005), at Harvard Medical School, carried out experiments to determine which level of processing within V1 was influenced by attention. Recall from Chapter 6 that many stages of neural processing take place within a visual area, and in V1 different neurons display characteristic receptivefield properties-some are called simple cells, others complex cells, and so on. Simple cells exhibit orientation tuning and respond to contrast borders (like those found along the edge of an object). Simple cells are also relatively early in the hierarchy of neural processing in V1- so, if attention were to affect them, this would be further evidence of how early in processing, and by what mechanism, spatial attention acts within V1. McAdams and Reid trained monkeys to fixate on a central point and covertly attend a black-and-white flickering noise pattern in order to detect a small, colored pixel that could appear anywhere within the pattern (Figure 7. When the monkeys detected the color, they were to signal this by making a rapid eye movement (a saccade) from fixation to the location on the screen that contained that color. The attended location would be positioned either over the receptive field of the V1 neuron they were recording or in the opposite visual field. Thus, the researchers could evaluate responses of the neuron when that region of space was attended and when it was ignored (in different blocks). They also could use the flickering noise pattern to create a spatiotemporal receptive-field map (Figure 7. In this way, the researchers could first determine whether the neuron had the properties of simple cells. A red bar is an effective sensory stimulus, and a green bar is an ineffective sensory stimulus for this neuron.

One method used with epilepsy patients compares their performance before and after surgery anxiety buy discount tofranil 50mg on-line. An especially fruitful paradigm for cognitive neuroscience has involved the study of patients who have had the fibers of the corpus callosum severed anxiety symptoms vs heart attack symptoms buy tofranil 25mg with visa. In these patients, the two hemispheres have been disconnected-a procedure referred to as a callosotomy operation or, more informally, the split-brain procedure. The relatively few patients who have had this procedure have been studied extensively, providing many insights into the roles of the two hemispheres on a wide range of cognitive tasks. In the preceding examples, neurosurgery was eliminative in nature, but it has also been used as an attempt to restore normal function. Although the standard treatment is medication, the efficacy of the drugs can change over time and even produce debilitating side effects. These devices produce continuous electrical signals that stimulate neural activity. There are side effects, in part because more than one type of neuron is stimulated. Optogenetics methods promise to provide an alternative method in which clinicians can control neural activity. Early work here suggests that the most effective treatments may not result from the stimulation of specific cells, but rather the way in which stimulation changes the interactions between different types of cells (Kravitz et al. This finding underscores that many diseases of the nervous system are not usually related to problems with neurons per se, but rather with how the flow of information is altered by the disease process. Methods to Perturb Neural Function As mentioned earlier, patient research rests on the assumption that brain injury is an eliminative process. The lesion is believed to disrupt certain mental operations while having little or no impact on others. The brain is massively interconnected, however, so just as with lesion studies in animals, structural damage in one area might have widespread functional. There is also increasing evidence that the brain is a plastic device: Neural function is constantly being reshaped by our experiences, and such reorganization can be quite remarkable following neurological damage. Consequently, it is not always easy to analyze the function of a missing part by looking at the operation of the remaining system. Many insights can be gleaned from careful observations of people with neurological disorders, but as we will see throughout this book, such methods are, in essence, correlational. Concerns like these point to the need for methods that involve the study of the normal brain. The neurologically intact participant, both human and nonhuman, is used, as we have already noted, as a control when studying participants with brain injuries. Neurologically intact participants are also used to study intact function (discussed later in this chapter) and to investigate the effects of transient perturbations to the normal brain, which we discuss next. One age-old method of perturbing function in both humans and animals is one you may have tried yourself: the use of drugs, whether it be coffee, chocolate, beer, or something stronger. Newer methods include transcranial magnetic stimulation and transcranial direct current stimulation. Genetic methods, used in animal models, provide windows into the molecular mechanisms that underpin brain function. We turn now to the methods used to perturb function, both at the neurologic and genetic levels, in normal participants. Single and double dissociations can provide evidence that damage to a particular brain region may result in a selective deficit of a certain cognitive operation. Studies conducted in patients before and after surgery have provided unique opportunities to study brainbehavior relationships. Methods to Perturb Neural Function 87 Pharmacology the release of neurotransmitters at neuronal synapses and the resultant responses are critical for information transfer from one neuron to the next. Pharmacological studies may involve the administration of agonist drugs, those that have a similar structure to a neurotransmitter and mimic its action, or antagonist drugs, those that bind to receptors and block or dampen neurotransmission.

With careful testing anxiety symptoms 7 months after quitting smoking 25mg tofranil with visa, doctors often can see residual signs of extinction anxiety symptoms muscle twitching tofranil 75 mg for sale, even after the most obvious signs of neglect have remitted as a patient recovers. This is one reason the condition is described as a bias, rather than a loss of the ability to focus attention contralesionally. Simultanagnosia is difficulty perceiving the visual field as a whole scene, such as when the patient saw only the comb or the spoon, but not both at the same time. Ocular apraxia is a deficit in making eye movements (saccades) to scan the visual field, resulting in the inability to guide eye movements voluntarily. The patterns of perceptual deficits are quite different, however, because different brain areas are damaged in each disorder. Neglect is the result of unilateral lesions of the parietal, posterior temporal, and frontal cortex. Neglect also can be due to damage in subcortical areas including the basal ganglia, thalamus, and midbrain. From patients with neglect, we understand that the symptoms involve biases in attention based on spatial coordinates, and that these coordinates can be described in different reference frames. Put another way, neglect can be based on spatial coordinates either with respect to the patient (egocentric reference frame) or with respect to an object in space (allocentric reference frame). This finding tells us that attention can be directed within space and also within objects. Indeed, the brain mechanisms involved with attending objects can be affected even when no spatial biases are seen. The phenomenon of extinction in neglect patients suggests that sensory inputs are competitive, because when two stimuli presented simultaneously compete for attention, the one in the ipsilesional hemifield will win the competition and reach awareness. Extinction also demonstrates that after brain damage, patients experience reduced attentional capacity: When two competing stimuli are presented at once, the neglect patient is aware of only one of them. It is important to note that none of these attentional deficits are the result of damage to the visual system per se, because the patient is not simply blind. These observations from brain damage and resultant attentional problems set the stage for us to consider several questions: Neglect is not the result of sensory deficits, because visual field testing shows that these patients have intact vision. Under the right circumstances, they can easily see objects that are sometimes neglected. A prominent feature of neglect is extinction, the failure to perceive or act on stimuli contralateral to the lesion (contralesional stimuli) when presented simultaneously with a stimulus ipsilateral to the lesion (ipsilesional stimulus). Neglect affects external personal hemispace and objects as well as internal memory for objects arrayed in space. Models of Attention When people turn their attention to something, the process is called orienting. The concept of orienting our selective attention can be divided into two categories: voluntary attention and reflexive attention. Voluntary attention is our ability to intentionally attend to something, such as this book. It is a goal-driven process, meaning that goals, knowledge, or expectations are used to guide information processing. Reflexive attention is a bottom-up, stimulus-driven process in which a sensory event-maybe a loud bang, the sting of a mosquito, a whiff of garlic, a flash of light or motion-captures our attention. As we will see later in this chapter, these two forms of attention differ in their properties and perhaps partly in their neural mechanisms. We all know what overt attention is-when you turn your head to orient toward a stimulus, whether it is for your eyes to get a better look, your ears to pick up a whisper, or your nose to sniff the frying bacon-you are exhibiting overt attention. You could appear to be reading this book, however, while actually paying attention to the two students whispering at the table behind you. Hermann von Helmholtz and Covert Attention In 1894, Hermann von Helmholtz (Figure 7. He constructed a screen on which letters were painted at various distances from the center (Figure 7. He hung the screen at one end of his lab and then turned off all the lights to create a completely dark environment.

The differences are primarily in their structure and pharmacokinetic profile; however anxiety xyrem quality tofranil 50 mg, to date none of these differences has been shown to be of clinical importance anxiety symptoms for years tofranil 25mg cheap. All appear to accomplish this maximally, and differences among the relative potencies are unimportant at the recommended doses. There is no clear evidence that one of these agents will be effective when another is not. Half-lives in the serum vary from approximately 3 to 11 hours, but activity at the receptor appears to be similar in that single doses of all agents are equally effective. From current trials, it appears that maximal benefit occurs once all relevant receptors are saturated. No matter what the emetic source, if the best results are to be achieved, an adequate dose should be given. Several international consensus guidelines have been published, including those from the subcommittee for antiemetics of the Multinational Association of Supportive Care in Cancer, those from the American Association of Clinical Oncology, and those from the American Society of Health-Systems Pharmacists. As a general rule, the lowest adequately tested dose should be assumed to be the best dose in all settings (Table 55. Doses, Schedules, and Classes of Commonly Administered Antiemetics Although some debate persists concerning the best dose of ondansetron, the majority of trials have indicated that the lower dose (8 mg) is as effective as the higher and far more expensive dose of 32 mg. Central nervous system effects, extrapyramidal reactions, and sedation are not observed with serotonin antagonists; this is particularly beneficial in younger patients. Common side effects include mild headaches usually not requiring treatment, transient transaminase elevations, and mild constipation with some agents. Dexamethasone is the best studied of all these agents, is available in oral and parenteral preparations and, in most countries, is very inexpensive. Although the best dose has not been established, it appears that a single 20-mg dose is adequate, with no clear indication that either higher or lower doses is preferred. Caution must be used when treating diabetic patients or others with poor tolerance for corticosteroids. However, the short recommended course makes these agents very safe and easy to use. In preventing delayed emesis, adequate doses of corticosteroids currently are viewed as the starting point of treatment, with some studies showing advantage for metoclopramide combined with steroids. This is seen with cisplatin chemotherapy99,100 as well as with such drugs as anthracyclines, cyclophosphamide, and carboplatin. In general, this efficacy is substantially lower than that seen with the serotonin antagonists (including high-dose metoclopramide), and the side effects are greater. Oral forms of all three of these agents exhibit only modest activity and are of similarly low efficacy. Several cannabinoids have been tested in chemotherapy-induced emesis and are of both historic and lay press interest. Antianxiety agents, such as the benzodiazepine lorazepam, have little efficacy as single agents in carefully conducted trials. It is not clear that there is any advantage in giving these agents parenterally rather than orally when given with the most effective antiemetics. Additionally, these drugs may be useful when given to patients with anticipatory emesis, starting one or more days before the next chemotherapy dosing. Side effects mainly concern sedation, which can be marked in some patients, especially if the drug is given intravenously (see Table 55. To date, the pathophysiology of this especially difficult problem remains unclear. What is known, however, is that delayed emesis is a phenomenon observed in as many as 80% of patients, typically occurring 24 to 72 hours after high total doses of cisplatin (>100 mg/m 2) have been administered. A study that outlined the natural history of delayed emesis concluded that although the emesis associated with this dilemma is less severe than that which is seen in the acute phase, it still poses significant problems with nutrition, hydration, and, possibly, a prolonged hospital course. Initial studies revealed that delayed emesis could be controlled with a regimen of metoclopramide and dexamethasone (Table 55.

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